This study was carried out during years of 1993-1999 at the Department of Medicine, Division of Endocrinology, University of Helsinki and at the Department of Human Molecular Genetics, National Public Health Institute. Professor Marja-Riitta Taskinen, M.D., the Head of the Division of Endocrinology is highly acknowledged for providing me excellent laboratory facilities and for continuous support in my efforts.

I express my greatest gratitude to my supervisors Raili Kauppinen and Leena Palotie-Peltonen. Raili has patiently taught me all the laboratory skills and the scientific way of thinking, although I was not always an especially quick learner. Her overwhelming enthusiasm towards porphyrias and molecular genetics has been contagious. Leena amazes me time and time again with her incredible memory and thorough knowledge of molecular genetics. Even though her schedule is very tight, she always found a time for me in her diary. After a meeting with Leena all problems whatsoever seemed much smaller.

Professors Marja-Liisa Savontaus and Jean-Charles Deybach reviewed this thesis. They gave constructive criticism and noted important weaknesses in it. I appreciate their careful examination of this manuscript and most of all their positive attitude towards my work.

I am more than grateful to my uncle Pertti Mustajoki, M.D., who originally introduced me to the world of porphyrias. Pertti's exceptionally wide perspective over the disorders of the heme metabolism is admirable. His supportive attitude towards my research has encouraged me repeatedly. Furthermore, our discussions have greatly influenced my way of working not only as a researcher but also as a practicing physician.

I would like to warmly thank all my collaborators Anu Wartiovaara (Suomalainen), M.D., Minna Laine (Peltola), M.D., Maija Lahtela-Kakko, Ph.D., and the members of the Danish Porphyria Research Laboratory: Henrik Nissen, Ph.D., Niels Erik Petersen, Ph.D., Torben Hansen, Ph.D., and Mogens Hørder, Ph.D. Their excellent knowledge and skills have considerably helped me during this study. Professor Bernard Grandchamp, M.D. is acknowledged for providing us with the PBGD cDNA and Dr. Ylva Floderus, PhD., provided us with PBGD antibody, which is also highly appreciated.

I warmly thank Ms. Hannele Pihlaja and Ms. Helena Ahola for their excellent technical assistance and always positive and flexible attitude. The intensive moments of laboratory work were made very pleasant when I could engage in interesting conversations concerning almost everything in the whole wide world. Although I did not have any direct collaboration with Dr. Kaisa Timonen, M.D., I found her presence in the porphyria research group very pleasant. Professor Raimo Tenhunen, M.D. is acknowledged for providing the facilities for enzyme activity measurements.

The colleagues and laboratory personnel in the Scientific Laboratory of the Helsinki University Central Hospital are warmly acknowledged for giving relaxing and hilarious company during the coffee-breaks, which too often were extended to coffee-hours. The atmosphere in the coffee-room of the Scientific Laboratory was exceptional, and that repeatedly cheered me up after an unsuccessful experiment. Especially I want to thank Ms. Sirkka-Liisa (Kikka) Runeberg, whose sense of humor and exceptional ability to listen have made a deep and ever-lasting impact on me.

I want to express my warmest gratitude to my other uncle professor Arto Mustajoki, Ph.D. The weekly squash matches, followed by the 'hair-drying', i.e. beer or two in the pub nearby, are unforgettable. Although the world did not become any better place to live despite our serious efforts, our conversations offered me fresh perspectives to the scientific world, especially from the linguistic and administrative point of view.

I have spent many breathtaking moments with the running team of the Scientific laboratory. The gentle pressure of the other regular members of the team, Satu Vehkavaara, Tatu Miettinen, Jaakko Kaukonen, Nina Lindbohm, and Heikki Relas, made me to take care of my physical wellbeing. Besides, no one else but a young researcher can really understand the difficulties of a young researcher, and our conversations during the weekly runs were often very therapeutic. Furthermore, I am pleased that the Scientific Losers Club was finally founded, although the two founder members, Jaakko and I, do not actually meet the criteria for the membership any more.

I have a wonderful family. My parents Erkki Mustajoki and Päivi Lindstedt have given me all the love and support I have ever needed. The importance of my two sisters, Henriikka Clarkeburn and Iida-Maaria Lindstedt, in my life cannot be exaggerated. The supportive attitude of Risto Lindstedt, Jeffrey Clarkeburn and my parents-in-law, Anna-Liisa and Olli Laurila, is also highly appreciated.

Finally, I am more than grateful to my wife Ulla. She has been there during all the phases of this work. She has patiently tolerated me when all went wrong in the lab and with her I have shared the moments of success. No words are sufficient to express my love to her.

This work was supported by grants from University of Helsinki, Academy of Finland, the Research Funds and the Clinical Research Institute of the Helsinki University Central Hospital, Emil Aaltonen Foundation, the Paulo Foundation, the Instrumentarium Foundation, the Science and Research Foundation of Farmos Medical Company, the Aarne Koskelo Foundation, and the Finnish Medical Society Duodecim.

Helsinki, October 1999

Sami Mustajoki